TREM1, or triggering receptor expressed on myeloid cells 1, is a cell surface receptor expressed on neutrophils, monocytes, and some tissue macrophages. It functions as an immunoregulator controlling myeloid cell responses. Once activated, it initiates downstream signaling pathways leading to the production of pro-inflammatory cytokines and chemokines, thus acting as an inflammation amplifier. It is involved in the pathogenesis of many inflammation-associated diseases [2].

In diabetes-associated cognitive impairment, lipophagy-induced microglial lipid droplets accumulation leads to the buildup of TREM1. Pharmacological blockade of TREM1 in db/db mice and HFD/STZ mice inhibited lipid droplets and TREM1 accumulation, reduced neuronal inflammatory damage, and improved cognitive functions, suggesting TREM1's role in this cognitive decline [1]. In cancer, TREM1-deficiency or blockade provides protection against tumors. For example, in murine melanoma and fibrosarcoma models, genetic or pharmacological TREM1 silencing significantly delayed tumor growth. TREM1 inhibition also enhanced the antitumorigenic effect of anti-PD-1 treatment by limiting MDSC frequency and abrogating T cell exhaustion [3].

In conclusion, TREM1 is a crucial immunoregulator that amplifies inflammation. Through gene-knockout mouse models and pharmacological inhibition, its role in diabetes-associated cognitive impairment and cancer has been revealed. In diabetes-related cognitive decline, it is involved in the lipophagy-related inflammatory process. In cancer, it promotes tumor progression, and its inhibition can enhance antitumor immunity, offering potential therapeutic targets for these diseases.